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Vaginal Hysterectomy Versus Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery Hysterectomy; Results of a Randomised Controlled Trial.

OBJECTIVE: To compare Vaginal Hysterectomy (VH) with Vaginal Assisted Natural Orifice Transluminal Endoscopic Surgery (NOTES) hysterectomy (VANH) as a day-care procedure. DESIGN: Single-blind, multicentre randomised controlled trial. SETTING: Two Dutch non-academic teaching hospitals. POPULATION: Women aged &#x2265;&#x2009;18&#x2009;years undergoing hysterectomy for benign indications. METHODS: Women were randomised 1:2 (VH or VANH). Primary outcome was SDD. Secondary outcomes included operative time, rate of elective salpingectomies, intraoperative blood loss, complications (Clavien-Dindo), pain scores (NRS) and analgesic use, post-operative recovery (RI-10), and quality of life (EQ-5D-5L). Analyses were performed on an intention-to-treat basis. RESULTS: A total of 113 patients were included in the analyses (n&#x2009;=&#x2009;42 VH, and n&#x2009;=&#x2009;71 VANH). SDD occurred significantly more frequently in the VANH group (87.3%) than VH group (71.4%; OR 2.76, 95% CI 1.04-7.25; p&#x2009;=&#x2009;0.04). VANH was associated with a significantly shorter operative time (median 55&#x2009;min versus 65&#x2009;min; p&#x2009;=&#x2009;0.005), less blood loss (median 50&#x2009;mL vs. 150&#x2009;mL; p&#x2009;<&#x2009;0.001) and more often elective opportunistic salpingectomy compared to VH (100% vs. 77.4%; p&#x2009;=&#x2009;0.008). NRS were significantly lower in the VANH group the first hour post-operative (3 vs. 1, p&#x2009;<&#x2009;0.001). Post-operative complications (VH 9.5% vs. VANH 15.5%; p&#x2009;=&#x2009;0.34), readmission (VH 4.8% vs. VANH 8.5%; p&#x2009;=&#x2009;0.47), analgesic use, recovery, and quality of life were not statistically significant. CONCLUSIONS: VANH is a safe and effective alternative to VH, offering a higher likelihood of SDD, shorter operative time, reduced blood loss, and more often an elective salpingectomy, without increased complications or differences in pain, recovery, or quality of life.

Humans

Endocrine Phenotypes and Hormonal Treatment in Meier-Gorlin Syndrome: Report of Two Cases and a Systematic Review of Literature.

BACKGROUND: Meier-Gorlin-syndrome (MGORS) is a rare cause of primordial dwarfism stemming from pathogenic variants in genes involved in DNA replication. The classic clinical triad is microtia, absent patella and short stature. MGORS can mimic endocrine causes of short stature or delayed/atypical pubertal development. METHODS: We report two new cases of MGORS. A systematic literature search of all cases published up to 31 March 2026 was done to identify the cases reporting any endocrinopathy or hormonal therapy, focussing on growth-hormone-deficiency (GHD) and response to growth hormone (GH). RESULTS: We describe a 14 year-old girl, the first MGORS case with CDC6 variant and mammary hypoplasia. Another 11-year old boy with GMNN variant had severe short-stature with GHD and had significant height improvement with GH. Among 29 cases (out of ~150 published), the classic triad was absent in 18.5%. Short stature was almost universal (median height-Z-score -4.4), with 70% exhibiting delayed bone age, 42.9% low IGF-1 and 35.3% GHD. Among 10 GH-treated cases with response data, 6 had reported improvement in height-SDS/growth-velocity. Those with GHD and delayed bone age were more likely to benefit from GH. Among females, all post-pubertal cases had mammary hypoplasia, while 23.5% had clitoromegaly with hypoplastic labia. Among males, cryptorchidism, hypoplastic scrotum and micropenis were common. However, gonadal hormones and gonadotrophins were normal. Data on the effect of estrogen on hypoplastic mammary glands or labia was variable. CONCLUSION: MGORS should be kept in mind as a differential of multiple endocrinopathies. Cases of MGORS should undergo screening for GHD. Available data, mostly from case-reports or small series, suggest that response to GH has been reported in some individuals, particularly where GHD or delayed bone age was present, but evidence remains very limited.

Humans

Prevalence of unruptured intracranial aneurysms according to comorbidities, risk factors, country, and time period: a systematic review and meta-analysis.

BACKGROUND: The incidence of aneurysmal subarachnoid haemorrhage declined between 1980 and 2010, which coincided with a decline in smoking and prevalence of hypertension. We aimed to investigate whether the decrease in subarachnoid haemorrhage incidence is paralleled by declines in unruptured intracranial aneurysm (UIA) prevalence. METHODS: For this systematic review and meta-analysis, we searched Embase, PubMed, and Web of Science for articles published in any language from Jan 1, 2011 to Dec 31, 2025, and reassessed 68 articles published before March 1, 2011 from a 2011 systematic review and meta-analysis. Articles were eligible for inclusion if they used a cross-sectional or case-control design and provided the crude number of participants and those with UIA. We only included studies reporting numbers of UIA separately from ruptured aneurysms and with ten or more patients. Summary data were independently extracted by JD with AZ or CB and conflicts were resolved by GJER. The primary outcome was proportion of participants with UIA. Relative to a hypothetical reference population (mean age 50 years, 50% women, and no comorbidities), age and/or sex-adjusted prevalence ratios (PRs) for regions, comorbidities, and risk ratios (RRs) for female sex, smoking, and hypertension were estimated using generalised linear mixed models. A time trend analysis was done by binomial meta regression using the mid-year of data acquisition. We assessed the certainty of evidence using GRADE. The study was registered with PROSPERO, number CRD420261296728. FINDINGS: Our search screened 4708 studies. 67 reassessed and 95 newly identified articles, reporting on 316&#x2008;131 participants and 11&#x2008;822 people with UIAs, were included in our meta-analysis. In the reference population, the estimated prevalence of UIAs was 3&#xb7;9% (95% CI 3&#xb7;0-5&#xb7;1). The prevalence of UIAs in individuals with atherosclerosis was 5&#xb7;5% (4&#xb7;7-6&#xb7;4; 2229 of 40970 participants) and the adjusted PR was 1&#xb7;3 (95% CI 0&#xb7;8-2&#xb7;0) compared with the reference population. For positive family history of aneurysmal subarachnoid haemorrhage (aSAH) or UIA, the UIA prevalence was 7&#xb7;9% (5&#xb7;6-11&#xb7;1; 412 of 4252 participants) and the adjusted PR was 2&#xb7;4 (0&#xb7;5-11&#xb7;2). For connective-tissue disorder, the UIA prevalence was 10&#xb7;3% (6&#xb7;5-16&#xb7;0; 94 of 879 participants) and the adjusted PR was 3&#xb7;9 (2&#xb7;0-7&#xb7;6). For autosomal dominant polycystic kidney disease (ADPKD), the UIA prevalence was 12&#xb7;8% (9&#xb7;2-17&#xb7;6; 293 of 1990 participants) and the adjusted PR was 4&#xb7;4 (1&#xb7;5-12&#xb7;6). RRs were for current smoking 1&#xb7;4 (1&#xb7;2-1&#xb7;6; 798 of 27911 participants), for having hypertension 1&#xb7;6 (1&#xb7;5-1&#xb7;7, 4043 of 83053 participants), and for female sex 1&#xb7;9 (1&#xb7;8-2&#xb7;0; 3415 of 65020 women and 2122 of 76130 men). In studies on healthy individuals with MR angiography or CT angiography as imaging modality, the prevalence in 2016-2022 was 6&#xb7;6% (6&#xb7;3-6&#xb7;8; 2904 of 41191 participants). The adjusted PR was 1&#xb7;8 (1&#xb7;1-2&#xb7;8) for 2016-2022 versus 2002-2015. Prevalence of UIAs of 5 mm or larger was 0&#xb7;7% (0&#xb7;6-0&#xb7;8) in 2002-2015 and 1&#xb7;4% (1&#xb7;0-1&#xb7;9) in 2016-2022. The UIA prevalence did not differ between countries. &#x3c4;2 showed significant heterogeneity between studies. The certainty of the evidence ranged from very low to moderate. INTERPRETATION: Prevalence of UIA is increasing, particularly over the past two decades. This increase is only in part explained by improved detection of small UIAs and an ageing population, and other factors-such as environmental-are likely involved. Alongside patients with ADPKD and a positive family history of aSAH, patients with connective-tissue disorders had a higher prevalence of UIA than the reference population. Our findings warrant further investigation into the potential benefit of personalised screening and management strategies in groups at high risk for having UIAs. FUNDING: None.

Humans

Efficacy and Safety of iGlarLixi Versus IDegAsp by Baseline Age, Disease Duration and HbA1c in Chinese People With Type 2 Diabetes: Post Hoc Analyses of the Soli-D Study.

AIMS: To compare the efficacy and safety of insulin glargine 100&#x2009;U/mL plus lixisenatide (iGlarLixi) with insulin degludec plus insulin aspart (IDegAsp) by baseline age, Type 2 diabetes (T2D) duration and glycated haemoglobin (HbA1c) in the Soli-D study. MATERIALS AND METHODS: In Soli-D, Chinese adults with T2D suboptimally controlled on oral antidiabetic drugs (OADs) were randomized to iGlarLixi or IDegAsp for 24&#x2009;weeks. These post hoc analyses evaluated glycaemic efficacy, insulin dose, body weight and hypoglycaemia outcomes in subgroups defined by baseline age (<&#x2009;65, &#x2265;&#x2009;65&#x2009;years), T2D duration (<&#x2009;10, &#x2265;&#x2009;10&#x2009;years) and HbA1c (&#x2265;&#x2009;7% to &#x2264;&#x2009;8% [&#x2265;&#x2009;53 to &#x2264;&#x2009;64&#x2009;mmol/mol], >&#x2009;8% to &#x2264;&#x2009;9% [>&#x2009;64 to &#x2264;&#x2009;75&#x2009;mmol/mol], >&#x2009;9% [>&#x2009;75&#x2009;mmol/mol]). RESULTS: Among 582 participants (iGlarLixi n&#x2009;=&#x2009;291; IDegAsp n&#x2009;=&#x2009;291), baseline age was <&#x2009;65&#x2009;years in 442 and &#x2265;&#x2009;65&#x2009;years in 140; T2D duration was <&#x2009;10&#x2009;years in 366 and &#x2265;&#x2009;10&#x2009;years in 216; and HbA1c was &#x2265;&#x2009;7% to &#x2264;&#x2009;8% in 205, >&#x2009;8% to &#x2264;&#x2009;9% in 209 and >&#x2009;9% in 168. At Week 24, HbA1c reductions were greater with iGlarLixi versus IDegAsp, with no treatment-by-subgroup interactions for baseline age, T2D duration or HbA1c. Change in other glycaemic outcomes, insulin dose and body weight generally showed no interaction across subgroups. Total insulin daily doses during treatment and hypoglycaemia event rates were consistently lower with iGlarLixi versus IDegAsp in all subgroups. CONCLUSIONS: iGlarLixi provides improved glycaemic control at lower insulin doses with reduced risk of hypoglycaemia in Chinese adults with suboptimally controlled T2D on OADs, regardless of baseline age, disease duration or HbA1c.

Humans

Clopidogrel Versus Dual-Antiplatelet Therapy for Long-Term Maintenance After Coronary Stenting in Ischemic and Bleeding Birisk Patients With Acute Coronary Syndromes and Diabetes: A Prespecified Subgroup Analysis of the OPT-BIRISK Trial.

BACKGROUND: Among patients with acute coronary syndromes at both high bleeding and ischemic risk (birisk), extended clopidogrel monotherapy after 9 to 12&#x2009;months of dual-antiplatelet therapy reduces bleeding without increasing ischemia. Whether this benefit extends to birisk patients with diabetes is unknown. METHODS: This prespecified subgroup analysis of the OPT-BIRISK (Optimal Antiplatelet Therapy for High Bleeding and Ischemic Risk Patients) trial included birisk patients with acute coronary syndrome who had completed 9 to 12&#x2009;months of dual-antiplatelet therapy after percutaneous coronary intervention. Patients were then randomized 1:1 to 9&#x2009;months of clopidogrel&#x2009;plus&#x2009;placebo versus clopidogrel&#x2009;plus&#x2009;aspirin. Outcomes were compared by diabetes status. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding at 9 months after randomization. The key secondary end point was major adverse cardiac and cerebral events, defined as a composite outcome of all-cause death, myocardial infarction, stroke, or clinically driven revascularization. RESULTS: Of 7758 patients, 4072 (52.5%) had diabetes. Clopidogrel monotherapy decreased Bleeding Academic Research Consortium type 2, 3, or 5 bleeding (2.1% versus 3.2%; hazard ratio [HR], 0.66 [95% CI, 0.45-0.97]) with no increase in major adverse cardiac and cerebral events (2.9% versus 3.6%; HR, 0.79 [95% CI, 0.56-1.12]) compared with clopidogrel plus aspirin in patients with diabetes. Outcomes were consistent in patients without diabetes, with no significant interactions by diabetes status. CONCLUSIONS: In birisk patients with acute coronary syndrome who were stable on dual-antiplatelet therapy with clopidogrel plus aspirin for 9 to 12 months after percutaneous coronary intervention, clopidogrel monotherapy for an additional 9 months reduced clinically relevant bleeding without increasing ischemic events compared with continued dual-antiplatelet therapy, irrespective of diabetes status. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT03431142.

Aged

Efficacy and Safety of Bimagrumab in Adults With Obesity and Metabolic Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

AIMS: This study aims to systematically evaluate the efficacy of bimagrumab on body composition and glucose parameters in adults with obesity and metabolic dysfunction and its safety profile. METHODS: We searched MEDLINE, PubMed, Embase, and the Cochrane Library on April 20, 2026, for randomized controlled trials (RCTs) assessing bimagrumab treatment in adults with obesity, insulin resistance, or type 2 diabetes mellitus (T2DM). The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and meta-analyses of efficacy and safety data were conducted using R software. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system was used to assess the strength of evidence. The study was registered with PROSPERO (CRD420261377110). RESULTS: Of the 134 retrieved records, 4 RCTs (enrolling 268 participants) were included. The included population represented a broad spectrum of metabolic dysfunction, from obesity and nondiabetic insulin resistance to established T2DM. Compared with placebo, bimagrumab treatment significantly reduced total weight (mean difference [MD] -4.85&#x2009;kg, 95% confidence interval [CI] -6.82 to -2.88), fat mass (-4.72&#x2009;kg [-8.05 to -1.40]), and glycated haemoglobin (HbA1c) (-0.13% [-0.23 to -0.03]) and significantly increased total lean mass (1.66&#x2009;kg [0.81 to 2.51]). However, bimagrumab led to an increase in low-density lipoprotein (LDL) concentrations of 0.47&#x2009;mmol/L [0.03 to 0.91] and significantly increased incidences of discontinuation (risk ratio [RR] 5.75 [1.61 to 20.46]), muscle spasms (RR 10.44 [4.23 to 25.75]), and diarrhoea (RR 4.91 [2.38 to 10.11]). CONCLUSION: Bimagrumab effectively reversed adverse effects on body composition in obese individuals, resulting in significant fat reduction, increased skeletal muscle mass, and improved glycemic control, suggesting that bimagrumab is a promising new target for personalized metabolic therapy.

Humans

Associations of Illness Perception, Resignation Coping, and Social Support With Self-Regulatory Fatigue in Patients With Type 2 Diabetes: A Cross-Sectional Study.

AIMS: To examine the associations among illness perception, resignation coping, social support, and self-regulatory fatigue (SRF) in patients with Type 2 diabetes mellitus. The study specifically explores whether resignation coping and social support exhibit indirect associations with SRF in the context of illness perception. DESIGN: A cross-sectional study. METHODS: From November 2024 to October 2025, a convenience sample of 302 adult patients with T2DM was recruited from a tertiary general hospital in China. Participants completed validated instruments with established psychometric properties, namely the Brief Illness Perception Questionnaire, the Medical Coping Modes Questionnaire, the Perceived Social Support Scale, and the Self-Regulatory Fatigue Scale. Statistical analyses included Spearman correlation and serial mediation analysis using the PROCESS Macro (Model 6) with bias-corrected bootstrapping. RESULTS: SRF was positively correlated with negative illness perception (r&#x2009;=&#x2009;0.579, p&#x2009;<&#x2009;0.01) and resignation coping (r&#x2009;=&#x2009;0.612, p&#x2009;<&#x2009;0.01), and negatively correlated with social support (r&#x2009;=&#x2009;-0.598, p&#x2009;<&#x2009;0.01). Serial mediation analysis revealed that illness perception was associated with SRF through indirect pathways involving resignation coping and social support. Resignation coping and social support mediated the association between illness perception and self-regulatory fatigue, both individually and sequentially. CONCLUSIONS: Negative illness perception correlates with higher SRF. This observed correlation is additionally linked to indirect pathways involving resignation coping and lower social support. Collectively, these findings highlight a pattern of interrelated cognitive (illness perception), behavioural (resignation coping), and resource (social support) factors that are associated with self-regulatory fatigue in this cross-sectional study. IMPLICATIONS FOR THE PROFESSION: The findings offer a clear, evidence-based framework for nursing practice. They highlight the potential value of integrated assessment and intervention that simultaneously addresses patients' illness beliefs, maladaptive coping strategies, and social support systems, which are associated with lower SRF and better diabetes self-management. REPORTING METHOD: This study adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cross-sectional studies. PATIENT OR PUBLIC CONTRIBUTION: Patients participated solely as research participants by providing survey data. They were not involved in the study design, implementation, data analysis, interpretation, or manuscript preparation. All patients provided written informed consent prior to questionnaire completion.

Humans

Naltrexone Is Superior to Placebo for Abstinence and Craving Reduction in Alcohol-Associated Cirrhosis: NAL-CI Trial.

BACKGROUND AND AIMS: Alcohol use disorder (AUD) coexisting with cirrhosis carries high morbidity and mortality, with no approved pharmacotherapy for AUD. We evaluated the safety and efficacy of naltrexone, an opioid receptor antagonist, in patients with compensated alcohol-associated cirrhosis (AaC) and AUD. METHODS: One hundred patients with compensated AaC and DSM-5 AUD were randomised 1:1 to naltrexone (50&#x2009;mg/day) or placebo for 12&#x2009;weeks. The primary endpoint was point-prevalence abstinence at 12&#x2009;weeks, defined as no alcohol use in the four preceding weeks. Secondary endpoints included craving (Obsessive Compulsive Drinking Scale [OCDS]-Obsessive and Compulsive subscales), lapses, relapses, and hepatic safety. Standardised psychosocial support was provided to both arms. RESULTS: Baseline characteristics were well matched between groups (mean MELD 12.6 vs. 12.7; CTP score 5.9 vs. 6.2; age 42.9 vs. 44.3&#x2009;years). AUDIT and OCDS scores were comparable between groups. Abstinence at 12&#x2009;weeks was significantly higher with naltrexone: 64% (32/50) versus 22% (11/50), p&#x2009;<&#x2009;0.001; OR 10.86 (95% CI: 1.89-62.2). Naltrexone significantly reduced lapses at 3&#x2009;months (28% vs. 54%, p&#x2009;=&#x2009;0.008) and showed a trend toward fewer heavy-drinking relapses (12% vs. 28%, p&#x2009;=&#x2009;0.07). Maintenance of abstinence at 6&#x2009;months favoured naltrexone (22% vs. 8%, p&#x2009;=&#x2009;0.09). No patient developed hepatic decompensation attributable to study medication, and no AST/ALT elevation exceeding 5&#xd7; ULN was observed in either group. Mean craving scores were lower with naltrexone by week 12 than with placebo: OCDS-O score (6.63&#x2009;&#xb1;&#x2009;1.16 vs. 9.29&#x2009;&#xb1;&#x2009;1.78, p&#x2009;<&#x2009;0.01) and OCDS-C score (6.35&#x2009;&#xb1;&#x2009;1.23 vs. 9.02&#x2009;&#xb1;&#x2009;1.86, p&#x2009;<&#x2009;0.01). Adverse events were comparable between the groups. CONCLUSION: Naltrexone is safe and effective in patients with compensated alcohol-associated cirrhosis, achieving a threefold higher abstinence rate and significantly reducing craving compared with placebo. These findings support the use of naltrexone as a pharmacological option in patients with compensated AaC and AUD. TRIAL REGISTRATION: NCT04391764.

Humans

Adolescents' Growing Sensitivity to Psychosocial Stressors: Evidence From Two Decades of Health Behaviour in School-aged Children (HBSC) Data in the Nordic Countries.

PURPOSE: We tested a perception-based explanation for rising psychosomatic complaints among adolescents in the Nordic countries. Specifically, we examined whether adolescents have become more sensitive to psychosocial stressors, reflected in stronger associations between stressors and psychosomatic complaints in 2022 than in 2002. METHODS: Data were drawn from the 2002 to 2022 waves of the Health Behaviour in School-aged Children survey among 15-year-olds in five Nordic countries (N = 7,263 in 2002 and 6,739 in 2022). Psychosomatic complaints were examined in relation to stressors in the following three domains: interpersonal relationships, school-related strain, and body- and activity-related factors. Moderated regression analyses tested whether associations between stressors and complaints differed between survey years. Sex and perceived family finances were included as covariates. RESULTS: Four of five psychosocial stressors showed stronger associations with psychosomatic complaints in 2022 than in 2002. Perceived poor family finances, although less prevalent in 2022, were more strongly related to complaints. Girls consistently reported higher levels of psychosomatic complaints, and the association between school pressure and complaints was stronger among girls. DISCUSSION: Although several psychosocial stressors declined in prevalence, their associations with psychosomatic complaints strengthened over time. These findings suggest that rising complaints may reflect changes in how psychosocial stressors are linked to adolescents' psychosomatic symptoms, rather than increases in exposure to those stressors. This shift highlights the importance of considering how adolescents interpret and respond to everyday stress when addressing population trends in mental health.

Humans

Phase IIB, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Intravenous Defibrotide for the Prevention and Treatment of Respiratory Distress and Cytokine Release Syndrome in COVID-19.

INTRODUCTION: Endothelial dysfunction is key in COVID-19 pathogenesis. This randomized, double-blind phase IIb trial investigated continuous intravenous infusion of defibrotide in patients hospitalized with SARS-CoV-2 infection and respiratory failure. METHODS: One-hundred and fifty patients were randomized (2:1) to defibrotide or placebo, stratified by disease severity (WHO COVID-19 severity scale 4/5 vs. 6). The primary endpoint was clinical improvement time (days from first improvement through Day 30). RESULTS: Median clinical improvement time was not significantly different with defibrotide versus placebo (15.0 [IQR: 0-24] vs. 20.0 [IQR: 9-25] days; p&#x2009;=&#x2009;0.10). Day-30 (23.0% vs. 22.0%) and Day-60 (26.0% vs. 22.0%) mortality, reduction in mean fraction of inspired oxygen during treatment, and median duration of hospitalization did not differ with defibrotide versus placebo. Defibrotide demonstrated favorable safety, with no differences versus placebo in serious adverse events (34.0% vs. 36.0%), hypotension (16.0% vs. 12.0%), or hemorrhage (13.0% vs. 8.0%). Exploratory pre-specified biomarker analyses showed greater early d-dimer reduction and lymphocyte recovery with defibrotide, although these results require validation. CONCLUSION: Continuous intravenous infusion of defibrotide was safe but did not improve clinical outcomes in severe COVID-19. Further analyses will explore mechanistic actions and pharmacokinetics of defibrotide and the pathophysiology of endothelial dysfunction in COVID-19. TRIAL REGISTRATION: EudraCT identifier: 2020-001409-21. CLINICALTRIALS: gov identifier: NCT04348383.

Adult

Adding Rib Mobilization to Diaphragm Release Techniques in Patients With Non-Specific Neck Pain: Randomized Controlled Trial.

BACKGROUND: Non-specific neck pain (NSNP) is a frequent issue that can negatively affect both mobility and function. Recently, there has been growing interest in newer therapeutic approaches, including rib mobilization and diaphragm release techniques, as potential ways to address NSNP and support better outcomes for those affected. PURPOSE: To find out the immediate effects of how (DRT) combined with (RMT) affects the level of pain and the extent to which patients' functional abilities are improved in cases of NSNP. METHODS: For this prospective RCT, 96 participants aged 20 to 45&#xa0;years were randomly assigned to one of three equal groups based on their pain score (VAS). Group B engaged in (DRT) for 40&#xa0;minutes, three times weekly for 8&#xa0;weeks, in contrast to Group A, which got both RMT combined with DRT. Group C (active control) received advice and some exercises. Measurements were collected before and after the intervention; the primary outcomes included pain severity, evaluated using a visual analog scale (VAS); active neck range of motion (ROM), measured with a cervical range of motion (CROM) device; and neck flexion endurance. Additionally, the secondary outcome of neck-related disability was assessed using the Neck Disability Index (NDI). RESULTS: No statistically significant difference was identified among the three groups at baseline; nevertheless, a treatment effect emerged after 8&#xa0;weeks (p&#xa0;=&#xa0;0.001 and f-value&#xa0;=&#xa0;4.15, &#x19e;2&#xa0;=&#xa0;0.306). A statistically significant time-treatment interaction was seen when comparing the pre- and post-treatment periods in groups A and B (p&#xa0;=&#xa0;0.001, f-value&#xa0;=&#xa0;3.16, &#x19e;2&#xa0;=&#xa0;0.251). CONCLUSION: The addition of rib mobilization to diaphragm release techniques in patients with non-specific neck pain resulted in statistically significant improvements in pain intensity, cervical flexion, right lateral rotation, left lateral rotation, right rotation, and neck flexor endurance, with moderate to large effect sizes for pain reduction and cervical motion. However, no statistically significant differences were observed between groups for cervical extension, left rotation, or the Neck Disability Index (NDI), and only a marginal clinical improvement in NDI was noted in Group A. The observed benefits in the combined intervention group may not be attributable solely to rib mobilization. The increased treatment complexity and greater therapist interaction inherent in the combined approach could also have influenced the outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07133646.

Humans

Global Seroprevalence of Q Fever Antibodies to Coxiella burnetii in Children and Adolescents : A Systematic Review and Meta-analysis.

OBJECTIVE: To comprehensively determine global estimates of Q fever seroprevalence in children and adolescents by conducting a systematic review and meta-analysis. DATA SOURCES: Searches of published articles in MEDLINE, Embase and Scopus databases were conducted from inception until February 2025. STUDY SELECTION: Cross-sectional studies reporting seroprevalence of Q fever/ Coxiella burnetii antibodies, using any established laboratory test, in any population of healthy children and adolescents <20 years old were included. The quality of eligible articles was assessed using a modified Newcastle-Ottawa Scale. DATA EXTRACTION: Data from eligible articles were extracted using a standardized form, which included year of publication, year(s) the study was conducted, numbers of antibody-positive cases/specific population, age, country, geographic region, serology test used and antibody titer cutoff value. DATA SYNTHESIS: DerSimonian and Laird random effects models were used to calculate pooled seroprevalence estimates and 95% confidence intervals in data from 41 eligible articles reporting 42 studies comprising 9841 children and adolescents. Q fever seroprevalence was observed in multiple countries across 7 geographic regions, and varied markedly between countries and regions, with the highest estimate observed by an individual country in Ethiopia (45%) and by region in the Middle East (14%). Seroprevalence estimates were higher in older children and adolescents &#x2265;10 years (15%) compared with younger children <10 years of age (8%). CONCLUSION: Despite varying geographical prevalence, our findings demonstrate that widespread exposure to Q fever antigens occurs across multiple global regions in children and adolescents to potentially serious C. burnetii infection, indicating that diagnostic surveillance and preventive measures should be considered in both endemic and previously unreported areas.

Humans

Genital surgery in children with differences of sex development (DSD): Strengths and concerns across diverging regulations in four European countries.

Differences of Sex Development (DSD) is a collective term for a heterogeneous group of rare congenital conditions characterized by atypical genetic, gonadal, or genital sexual development. The treatment of children with DSD, particularly the indications for and timing of surgical interventions, has been the subject of debate for decades. In recent years, social developments emphasizing children's rights to self-determination and bodily integrity, along with increasing societal acceptance of atypical sex characteristics, have encouraged a more cautious approach toward early genital surgery in children with DSD. In 2019, the European Parliament adopted a resolution urging Member States to enact legislation prohibiting elective genital surgical interventions on intersex infants and children. Since then, several countries have indeed implemented restrictive measures, including legal bans on early surgical procedures. In this paper, we share the experiences and insights gained in recent years as pediatric urologists working in four neighboring countries in multidisciplinary university centers specializing in DSD care and research. We focus on current approaches to the care of children with DSD, the evolution of relevant national policies over time, and the nature and impact of recently introduced restrictive regulations on early surgical interventions. By presenting perspectives from pediatric urologists across these four countries, we aim to contribute to ongoing discussions on the alignment and refinement of surgical treatment practices for children with DSD.

Humans

Influence of Concave Versus Convex Emergence Profiles on Midfacial Mucosal Stability-A Systematic Review With Meta-Analysis.

OBJECTIVES: To systematically evaluate the influence of concave versus convex emergence profiles on midfacial mucosal stability in partially edentulous patients restored with implant-supported single restorations. MATERIALS AND METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted and registered in PROSPERO (CRD420251139042). An electronic search in MEDLINE (PubMed) and Embase was performed up to May 7, 2026. Eligible studies included RCTs comparing concave (test group) and convex (control group) transmucosal prosthetic designs and reporting midfacial mucosal level changes (mm). Data extraction and risk of bias assessment (RoB 2) were performed independently. A random-effects meta-analysis was conducted using weighted mean differences (MDs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic and sensitivity analyses were performed to evaluate the robustness of the findings. RESULTS: Four RCTs including 144 implants with a 12-month follow-up were included. Of these, 128 implants contributed to the quantitative synthesis, with 66 implants allocated to the concave/modified emergence profile group and 62 implants allocated to the convex/non-concave emergence profile group. The pooled analysis demonstrated a mean difference of -0.31&#x2009;mm (95% CI -0.63 to 0.02; p&#x2009;=&#x2009;0.064), indicating a trend toward greater midfacial mucosal recession with convex emergence profiles compared with concave designs. Between-study heterogeneity was low to moderate (I2&#x2009;=&#x2009;28%), suggesting consistent findings across studies. Sensitivity analyses confirmed the direction of the effect, with pooled estimates ranging from -0.12 to -0.43&#x2009;mm. Exclusion of one study resulted in a statistically significant difference favoring concave emergence profiles (-0.43&#x2009;mm; 95% CI -0.70 to -0.16; p&#x2009;=&#x2009;0.002). CONCLUSIONS: Convex emergence profiles are associated with a tendency toward increased midfacial mucosal recession. Concave profiles are preferable to support peri-implant soft-tissue stability. CLINICAL RELEVANCE: Emergence profile design should be considered an integral component of prosthetic and surgical planning. The use of concave transmucosal contours during provisionalization and definitive restoration may contribute to improved peri-implant soft tissue stability and enhanced esthetic outcomes.

Humans

Effects of hospital planning reforms on access, costs, efficiency, and quality of care in OECD countries: Systematic review and meta-analysis.

BACKGROUND: Many OECD countries have implemented hospital planning reforms to rising healthcare costs, demographic changes, and concerns about access, efficiency, and quality of care. Despite broad implementation, evidence on effectiveness remains fragmented and country-specific. OBJECTIVE: To synthesize evidence on the effects of hospital planning reforms aross four outcome domains: access, costs, efficiency, and quality of care. METHODS: We conducted a systematic review following Cochrane methodology, searching PubMed and Web of Science (January 2000 - September 2025). Studies were categorized into four intervention types - centralization, minimum volume requirements (MVR), performance-based targets, and governance and ownership restructuring. Risk of bias was assessed using Joanna Briggs Institute checklist for quasi-experimental designs. Where data permitted, random-effects meta-analyses pooled standardized mean differences (SMD) for access and efficiency and risk differences (RD) for quality outcomes. RESULTS: 26 studies from 12 countries were included. Centralization increased patient travel distances and reduced length of stay (SMD -0.09, 95% CI -0.17 to -0.01) and complications (RD -14.52 pp, -25.95 to -3.09), and, jointly with performance-based targets, 30-day readmissions (RD -0.43 pp, -0.65 to -0.22). Mortality effects varied by timepoint and intervention: short-term endpoints were largely non-significant, whereas 90-day mortality was reduced under centralization (RD -0.80 pp, -1.25 to -0.35) and 60-day mortality under MVR (RD -2.00 pp, -2.82 to -1.18). Survival was non-significant throughout. No study examined costs. CONCLUSION: The absence of cost evidence is a critical gap. Substantial heterogeneity reflects variation in reform design and context, underscoring the need to interpret findings by intervention and country conditions.

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Attitudes, knowledge, and behavioral control regarding child abuse reporting in middle eastern nursing professionals: A systematic review and meta-analysis.

INTRODUCTION: Child abuse is critically underreported in the Middle East, with up to 90% of cases going unidentified. Nurses play a central role in child protection systems, yet factors influencing their reporting practices in this region have not been comprehensively synthesized. This study aims to review systematically and meta-analyze evidence on Middle Eastern nurses' knowledge, attitudes, and perceived behavioral control regarding child abuse reporting. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines. Five databases (PubMed, Scopus, Web of Science, Embase, Cochrane Library) were searched through November 2025. Studies targeting nursing professionals or students in Middle Eastern countries assessing knowledge, attitudes, intention to report, subjective norms, or perceived behavioral control were included. Random-effects meta-analyses were performed with subgroup analyses comparing students and practicing nurses. RESULTS: Fourteen studies comprising 4018 participants across six countries met the inclusion criteria. The pooled knowledge score was 61.64% (95% CI: 50.14-73.14), with nursing students scoring higher than practicing nurses (75.28% vs. 54.79%, p&#xa0;=&#xa0;0.03). The pooled attitude score was 60.69% (95% CI: 44.82-76.57). Educational interventions significantly improved knowledge (SMD&#xa0;=&#xa0;1.54, 95% CI: 0.70-2.38, p&#xa0;=&#xa0;0.0003). The pooled proportion of nurses intending to report suspected abuse was 75% (95% CI: 0.58-0.92). The pooled subjective norm score was 8.02 (95% CI: 7.75-8.29), and the pooled perceived behavioral control score was 24.34 (95% CI: 22.20-26.46). High heterogeneity (I2&#xa0;>&#xa0;95%) reflects substantial variability in educational and legal contexts across the region. CONCLUSIONS: Middle Eastern nurses show moderate knowledge and attitudes toward child abuse reporting, with notable gaps among practicing professionals. Educational interventions are effective but should be integrated with systemic reforms, including mandatory reporting legislation and clear protocols.

Humans

Vitamin D Deficiency During Pregnancy Is Associated With Greater LDL-C Increase, Elevated &#x3b2;-Hydroxybutyrate and Altered Neonatal Metabolic Markers-A Secondary, Pooled Analysis of the Randomized, Controlled Vitamin D and Lifestyle for Gestational Diabetes Prevention Trial (DALI).

INTRODUCTION: Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS: In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20&#x2009;weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age&#x2009;>&#x2009;=18&#x2009;years, singleton pregnancy, <&#x2009;20&#x2009;weeks' gestation, BMI &#x2265;&#x2009;29&#x2009;kg/m2. Women with GDM <&#x2009;20&#x2009;weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (<&#x2009;30&#x2009;nmol/L, n&#x2009;=&#x2009;102), insufficient (30-50&#x2009;nmol/L, n&#x2009;=&#x2009;222) and sufficient (>&#x2009;50&#x2009;nmol/L, n&#x2009;=&#x2009;638) groups. VitD levels and lipid concentrations were assessed at <&#x2009;20, 24-28 and 35-37&#x2009;weeks' gestation and in cord blood. RESULTS: Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and &#xdf;-OH-butyrate at 24-28&#x2009;weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher &#xdf;-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS: Early vitamin D deficiency before 20&#x2009;weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION: Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

Humans

Female genital mutilation knowledge, attitudes and training needs among health professionals in non-practicing countries: A literature review.

BACKGROUND: With increasing globalization and migration, the number of women affected by female genital mutilation who reside in countries where the practice is not traditionally performed is constantly increasing. Healthcare providers in these settings are required to address the complex health needs of this vulnerable population. We aimed to synthesize recent literature on their knowledge, preparedness, and educational background. METHODS: We conducted a systematic review across PubMed, Scopus and Embase, identifying papers published from January 2015 onwards, examining providers' knowledge, education and attitudes toward female genital mutilation in non-practicing countries. Both quantitative and qualitative observational studies were eligible. Given heterogeneity in study populations, outcome definitions, and assessment tools, findings were synthesized narratively. The review protocol was registered with the International Prospective Register of Systematic Reviews (CRD420251044761). FINDINGS: 1046 records were screened by title and abstract, and 140 full-text articles were assessed for eligibility. 31 studies met the inclusion criteria (23 quantitative, 8 qualitative). Many providers reported clinical experience with women affected by female genital mutilation, yet substantial variability was observed in knowledge, training, and attitudes. Gaps were particularly evident regarding legislation, World Health Organization classification, clinical guidelines, referral pathways, workplace protocols. Midwives and younger professionals tended to demonstrate higher knowledge levels. Training exposure ranged from 5% to 91%, and many participants perceived it as insufficient. Qualitative findings echoed these patterns, highlighting challenges in female genital mutilation classification, legal awareness, documentation systems, the impact of providers' cultural beliefs on care delivery. CONCLUSION: Considerable efforts are needed to equip healthcare providers to deliver high-quality, culturally competent care to women affected by female genital mutilation. Research should develop validated tools to assess preparedness, adopt mixed-methods strategies to capture patient and provider perspectives, and guide standardized, up-to-date training programs, strengthening knowledge in managing female genital mutilation.

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